The effects of both the long-acting thyroid stimulator (LATS) and pituitary thyrotropin (TSH) appear to be mediated by cyclic adenosine monophosphate (cAMP). We have developed an in vivo assay system for TSH and LATS in which changes in mouse thyroid cAMP are measured as an index of stimulation. We have shown that there are species differences in thyroid cAMP response to TSH and we propose to examine the mechanism of these differences. We have demonstrated that cAMP and cGMP can be localized by immunofluorescent staining techniques and we propose to examine the localization of the nucleotides further using immunoperoxidase staining techniques. We have demonstrated that there is a stimulator in LATS negative sera of patients with Graves' Disease and we propose to localize this stimulator in the serum and further characterize it.